Pentazocine and Naloxone Tablets
(Monograph under this new title—to become official February 1,2005)
(Current monograph title is Pentazocine and Naloxone Hydrochlorides Tablets)
»Pentazocine and Naloxone Tablets contain amounts of Pentazocine Hydrochloride and Naloxone Hydrochloride equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amounts of pentazocine (C19H27NO)and naloxone (C19H21NO4).
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Crush 1Tablet in 10mLof a mixture of chloroform and methanol (1:1),and mix.Sonicate for about 2minutes,and filter (Solution A).Evaporate 5mLof Solution Ato dryness on a steam bath under a stream of nitrogen.Dissolve the residue in 0.2mLof the mixture of chloroform and methanol (1:1)(Solution B).Apply 10µLof Solution A,5µLof Solution B,10µLof a Standard solution of USP Pentazocine RSin the 1:1mixture of chloroform and methanol containing 5.0mg per mL,and 5µLof a Standard solution of USP Naloxone RSin the 1:1mixture of chloroform and methanol containing 1.3mg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatograms in a solvent system consisting of a mixture of 1-butanol,water,and glacial acetic acid (70:20:10)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and dry under a current of warm air.Spray the plate with Folin-Ciocalteu Phenol TSfollowed by sodium hydroxide solution (1in 10).Tests Solution Aand Solution Bexhibit spots having the same RFvalues and approximately the same size and shape as their respective Standard solutions.
Dissolution á711ñ—
Medium: water;900mL.
Apparatus 2: 50rpm.
Time: 45minutes.
Procedure— Determine the amount of C19H27NOdissolved from UVabsorption at the wavelength of maximum absorbance at about 279nm (corrected for absorbance at 305nm)on filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Pentazocine RSprepared by dissolving the standard in a minimum volume of 0.1Nhydrochloric acid (about 4mLper 100mg)and diluting quantitatively and stepwise with water.
Tolerances— Not less than 75%(Q)of the labeled amount of pentazocine (C19H27NO)is dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY FOR PENTAZOCINE AND NALOXONE—
Solvent mixture— Use a mixture containing methanol,water,and phosphoric acid (500:500:1).
Mobile phase— Prepare a filtered and degassed mixture by dissolving 675mg of sodium 1-octanesulfonate and 426mg of anhydrous dibasic sodium phosphate in 625mLof water,and mix.Add 475mLof methanol and 10mLof phosphoric acid.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Strong anion-exchange resin— Transfer about 30g of strong anion-exchange resin to a 250-mLbeaker.Wash the resin with two 200-mLportions of water,decanting the water after each wash.Wash with two 200-mLportions of dilute glacial acetic acid (1in 20),decanting the first wash,and filter with the aid of suction.
Standard stock solution— Transfer about 20mg of USP Naloxone RS,accurately weighed,to a 100-mLvolumetric flask.Dissolve in and dilute with Solvent mixtureto volume,and mix.
Standard solution— Transfer about 100mg of USP Pentazocine RS,accurately weighed,to a 50-mLvolumetric flask.Dissolve in about 30mLof Solvent mixture.Add 5.0mLof the Standard stock solution,dilute with Solvent mixtureto volume,and mix.
Test solution— Transfer 1Tablet to a 25-mLglass-stoppered cylinder.Add 25.0mLof Solvent mixture.Sonicate for 10minutes,and shake intermittently for 15minutes.Filter into a glass-stoppered conical flask.Add about 125mg of Strong anion-exchange resin,and shake for 30minutes.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.3for naloxone and 1.0for pentazocine;the resolution,R,between pentazocine and naloxone is not less than 6;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,adjusting the operating parameters such that satisfactory chromatography and peak responses are obtained with the Standard solution.Record the chromatograms,and measure the areas for the major peaks.Calculate the quantities,in mg,of pentazocine (C19H27NO)and naloxone (C19H21NO4)in the Tablet taken by the same formula:
25C(rU/rS),
in which Cis the concentration,in mg per mL,of the appropriate USP Reference Standard in the Standard solution;and rUand rSare the peak responses for the corresponding analyte obtained from the Test solutionand the Standard solution,respectively.
Assay for pentazocine and naloxone— Proceed as directed for Procedure for content uniformity for pentazocine and naloxone,except to use the following Assay preparationin place of the Test solution,and to prepare the Standard preparation as directed for the Standard solution.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 100mg of pentazocine,to a 100-mLvolumetric flask,and add 50.0mLof the Solvent mixture.Sonicate for 5minutes,and shake intermittently for 15minutes.Filter into a glass-stoppered conical flask.Add about 250mg of Strong anion-exchange resin,and shake for 30minutes.
Procedure— Proceed as directed for Procedureunder Uniformity of dosage units.Calculate the quantities,in mg,of pentazocine (C19H27NO)and naloxone (C19H21NO4),in the portion of the finely powdered Tablets taken by the same formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of the appropriate USP Reference Standard in the Standard preparation;and rUand rSare the peak responses of the corresponding analyte obtained from the Assay preparationand theStandard preparation,respectively.
(Official February 1,2005)
Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1505
Pharmacopeial Forum:Volume No.28(6)Page 1846
Phone Number:1-301-816-8143